Githormones 20-21 Batch

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GIT

HORMONES

DR.UMADEVI.S.V.
OBJECTIVES

INTRODUCTION.
HISTORY.
CLASSIFICATION.
COMMON DESCRIPTION.
CELLS PRODUCING – SOURCE.
CLASSIFICATION.
LOCATION.
STIMULUS.
MECHANISM OF ACTION.
ACTIONS.
APPLIED.
INTRODUCTION
 Earlier ---Believed Regulatory mechanisms were
controlled by the nervous system

 Later numerous chemicals in the name of


hormones were found

 Hormones -- Play an integral role in most of the


regulatory mechanisms in our body

 Main objective of learning this topic in detail


INTRODUCTION. (Cont….)
PARACRINE HORMONES.

Largest endocrine organ


Enteric endocrine system.
Total about 30 GIT hormones.
These are biologically active
polypeptide & act in a paracrine
fashion.
Main function is:
1. To regulate the git secretion
2. To regulate the movement of GI
tract.
SITE OF ACTION.
Endocrine Autocrine Paracrine
HISTORY.
BAYLISS & STARLING (1902) discovered the first
GIT hormone secretin.
GREGORY AND TRACY (1964) --chemical definition
of Gastrin.
YALOW AND BENSON (1966) invented RIA to
estimate quantity .
JORPES AND MUTT (1996) chemical nature of
secretin and cholecystokinin and a group of other
hormones.
Endocrinal cells.
Origin - Neuroectodermal
Act - On surfaces
Mechanism - 1. Neurocrine
 2. Paracrine
 3. Classic endocrine
Endocrine cells - GIT

“Enteroendocrine cells”
 More than 15 types present
 Spread all over --stomach, small
intestine,
colon
 Many cells secrete only one
hormone
eg. G cells, S cells, K cells,
M cells
 Cells that manufacture Serotonin
in addition to polypeptides –
Entero- chromaffin cells.
APUD cells or Neuroendocrine cells
(Amine Precursor Uptake and
Decarboxylase).

 Cells that manufacture amines in addition


to polypeptides
 Found in lungs and other organs in addition
to GIT
 Can form carcinoid tumors
CLASSIFICATION

1. Secretin 1. Peptide YY
1. Gastrin
2. Glucagon 2. Ghrelin
2. Cholecystokinin
3. Glicentin 3. Motilin
(CCK)
4. VIP 4. Somatostatin
5. GIP 5. Neurotensin
6. Substance P
7. GRP
8. Bombesin
9. Glucagon
10. Guanylin
GASTRIN.
Source:
G cells (stomach pyloric antral
region)
Flask shaped, granules +
Also -- hypothalamus,
Pituitary –ant,
intermediate
Medulla,
Fetal pancreas,
Nerves --Vagus, sciatic
nerves
STRUCTURE:
APUD CELLS
polypeptide
3 types

G14 G17 G34

G17– Principal form


Half life 2-3 min
Metabolised – kidney, SI.

G cells
-secrete gastrin
G.I. HORMONES

Gastrin (17 AA)


Cholecystokinin (CCK (33 AA))

Structure of Secretin (27 AA)


(comparison with other GI hormones)
LOCATION.
STIMULATION FOR RELEASE
• “TASTE” – the luminal environment & Respond
STIMULATION HORMONES RELEASED

VAGAL STIMULATION, HCL & GASTRIN


PRODUCT OF DIGESTION
DIETARY PROTEIN GASTRIN & CCK

DIETARY CARBOHYDRATE GIP & GLUCAGON LIKE


SUBSTANCES
DIETARY FAT CCK & GIP

HYDROGEN IONS SECRETIN


STIMULATION OF GASTRIN
Stimulation increases
Luminal

* peptides & amino acids- phenylalanine &


tryptophan
* Distention of pyloric antrum.
Heidenhain pouch – denervated
antral pouch
Pavlov pouch – small pouch with
intact nerve & blood supply.
Neural

* vagal through GRP


Blood borne

* Calcium
* Epinephrine
DECREASES
 Blood borne
 Secretin
 Luminal
 VIP, GIP
 * Acid – by negative
feedback effect
 Glucagon

 * Somatostatin
 Calcitonin

Sunday, August 11, 2024


Mode of action
Gastrin Receptor (parietal cells)

Intracellular
calcium(IP3)
H+-K+ ATPase Ca++ activates
protein kinase

Acid secretion
Function of gastrin.
Stimulate Gastric Acid and pepsin secretion
Trophic action – growth of gastric mucosa and intestinal mucosa
Stimulate Gastric Motility
Contraction of muscle at gastro esophageal junction cardiac sphincter prevents
reflux oesophagitis

Peristaltic
contraction
Functions of Gastrin.
 Stimulate Exocrine pancreas secretion
 Stimulate Insulin secretion
 Stimulate mass movement of large
intestine
 Colonic contraction that initiates Gastro-
colic reflex – defecation after meal
 Stimulate Histamine secretion from ECL
cells
Food in the stomach Products of protein digestion Vagal stimulation
(gastric distension) (peptides and amino acids) (Non – cholinergic)

REGULATION G cells of stomach

Secretion of gastrin

Parietal cells of stomach

HCI secretion

Intestinal hormones
High acidic gastric content
Acidic duodenal chyme (GIP, VIP, somatostatin, secretin
(auto regulation of
gastrin secretion
(secrete hormones) & glucagon)
CHOLECYSTOKININ-pz.
GREEK –
chole, "BILE"; cysto, "SAC"; kinin, "MOVE"; so MOVE
THE BILE-SAC

Source: I cells – Granular mucosal cells of


duodenum & jejunum.
Also – cerebral cortex, somatic nerves,
distal ileum, colon.
STRUCTURE:

CCK 58 39 33 12 8 4

Stimuli: Acid, protein, fat


Digested products in duodenum

Initially considered 2 hormones later found to be


one
Functions of CCK-pz

Contraction of gall bladder –


increased bile release
Stimulate pancreatic secretion
rich in enzyme
Augments the action of secretin
Inhibit gastric acid secretion
Inhibit gastric motility
Delay gastric emptying
Regulation of secretions.
•CCK-PZ –
• Increased by
Acid in duodenum
Products of carbohydrates, fats, & proteins

digestion.
Mainly peptides & amino acids

Positive feedback–
SECRETIN.
Bayliss & Starling (1902)
discovered the first gastro
intestinal hormone SECRETIN

SOURCE : S cells – upper SI


(Argentaffin cells)
Structure : 27 AA
Stimuli : Acid in duodenum
Function of secretin.

Stimulate secretion of pancreatic juice rich in HCO3-


Stimulatebile secretion.
Augment action of CCK to produce pancreatic secretion rich in enzymes
Reduces the gastric acid secretion and motility
Contraction of pyloric sphincter
REGULATION OF SECRETION

HCL & MOTILITY

H
+ CL
Na
H
CO
Na 3
cl
,C
O
2,
H
2O NaHCO3
GASTRIC INHIBITORY
PEPTIDE( GIP)
 Source: K cells – jejunum & duodenum

 Initially called Enterogastrone.

 Discovered as a factor in extracts of


intestine that inhibited gastric motility
and secretion of acid.
GASTRIC INHIBITORY
PEPTIDE( GIP)
 Another activity of GIP is its ability to Enhance
the release of insulin in response to infusions of
glucose. -- Glucose-dependent insulinotropic
peptide.

 Regulation – Increases by fat in duodenum

Sunday, August 11, 2024


VASOACTIVE INTESTINAL POLYPEPTIDE (VIP)

 Source – Mucosal cells in jejunum

 Stimuli – fatty meal

 Structure -- polypeptide 28 amino acids

 Other sites—
 Nerves in GIT,
 Blood,
 Brain ( cerebral cortex)
 Autonomic nerves.
ACTIONS.
 Stimulate Intestinal secretion of electrolytes &
water.
 Vasodilatation – decreases BP
 Induce smooth muscle relaxation (lower
esophageal sphincter, stomach, gallbladder)
 Stimulate secretion of water into pancreatic
juice and bile.
 Inhibition of gastric acid secretion and
absorption from the intestinal lumen.
 Decreases the GI motility.
ENTEROGLUCAGON AND
GLUCAGON-LIKE PEPTIDES.
Source : Terminal SI and LI - L cells.
 Given the name "Enteroglucagon",
"Proglucagon-derived Peptides".
 In both pancreas and gut, 3 types of products are
generated:
• Glucagon-like Peptide-1 (GLP-1)
• Glucagon-like Peptide-2 (GLP-2)
• Glucagon-like Peptide-3 (GLP-3)

Sunday, August 11, 2024


GLP-1
 Inhibit gastric  Glucagon-like
emptying, peptide-2
 Inhibit gastric  It stimulates
secretion and proliferation of
 Inhibit pancreatic intestinal epithelial
secretion, cells.
 Decreases food
intake.

Sunday, August 11, 2024


SOMATOSTATIN (GHIH).
 Source -- S Cells or δ cells
 GIT MUCOSA.

 Structure– SS14, SS28 (more active)

 Somatostatin is also secreted by the Hypothalamus &


pancreas.
 Stimuli –
 Acid in stomach

 stimuli which increases insulin secretion

Sunday, August 11, 2024


ACTIONS
 Secretions of Gastrin, secretin, Motilin,

 Pancreatic – Exocrine & Endocrine secretions

 Gastric acid secretions & motility


( Dyspepsia & slow gastric emptying)

 Gall bladder contractions ( Precipitate gall stone)

 Absorption of glucose amino acid, & triglyceride.


MOTILIN
• Source -- Endocrinocytes (Mo Cells) in
the mucosa of the proximal Small Intestine.

• Based on 22 AA sequence,
MOTILIN

 MOTILIN participates in controlling the pattern of


smooth muscle contractions in the upper GI tract that
increases the MIGRATING MYOELECTRIC COMPLEX
("Housekeeping contractions“).

 It sweep the stomach and SI clear of undigested


material and stimulates the production of PEPSIN.
GHRELIN-28 AA
 ’Ghre’’ – Growth ---- Europian name.
 Source -- Endocrine cells in the stomach,
especially when one is hungry;
 Action-- acts on the hypothalamus to stimulate
feeding;

 This action counteracts the inhibition of feeding


by leptin and Pyy 3-36.

Sunday, August 11, 2024


GHRELIN-28 AA
GUANYLIN
 15 amino acid residues
 Source:
 Cells of the intestinal mucosa
 Stimulant:
 Stimulation of Guanylin
 Function:
 It increase Cl- movement to intestine
Other hormones
Hormones source Effects
Neurotensin Neurons & ileal Inhibit GI motility - ileal
epithelium blood flow
GRP Vagal nerve Gastrin release
Guanylin Paneth cells Secretion of chloride ions
Chymodenin Duodenal mucosa Selective secretion of
chymotrypsinogen from
pancreatic acinar cells
Substance P Entire GIT Increases the motility of SI
Increases local vasodilation
Perception of pain sensation
Bombesin Entire GIT Increases gastric secretion
Increases motility of gall
bladder
Increases motility of SI
SUMMARY OF ACTIONS
SUMMARY
APPLIED
PHYSIOLOGY.
ULCER

ZOLLINGER-ELLISON SYNDROME (GASTRINOMA)


Zollinger-EllisonSyndrome(Gastrinoma)

Caused by a tumor (or tumors) called

Gastrinoma gastrin stomach acid.

SIGNS & SYMPTOMS:


Pain in the stomach and esophagus,
Nausea
Vomiting of blood,
Difficulty in swallowing
Sore throat, coughing, and wheezing
Sour or bitter taste in the mouth
Blood in the stool
VERNER MORRISON SYNDROME
( VIPOMAS)
 VIP Cause profound and chronic
WDHA-syndrome (or)
pancreatic cholera syndrome
Watery Diarrhoea and resultant
Dehydration,
Hypokalemia,
Achlorhydria,
Acidosis,

 vasodilation (flushing and


hypotension),
Hypercalcemia
Hyperglycemia.
TREATMENT

Symptomatic

control
Somatostatin

analogues
Resection

VERNER MORRISON SYNDROME


CARCINOID TUMORS( APUDOMAS)
Carcinoid tumors originate from the diffuse
neuroendocrine system, specifically the
enterochromaffin (EC) cells (submucosa of the
intestine)
Gastrointestinal Peptides and Amines
Secreted by Carcinoid Tumors
 ACTH
 Gastrin
 Pancreatic polypeptide
 Insulin
 Vasoactive intestinal polypeptide (VIP)
 Serotonin
 5-hydroxyindoleacetic acid

Sunday, August 11, 2024


INTRODUCTION SUMMARY
HISTORY
COMMON DESCRIPTION
CELLS PRODUCING
CLASSIFICATION
LOCATION
STIMULUS
MODE OF ACTION
DETAIL ABOUT EACH HORMONES
GASTIN
CHOLECYSTOKININ
SECRETIN
MOTILIN
VASOACTIVE INTESTINAL
POLYPEPTIDE
GASTIC INHIBITORY
POLYPEPTIDE
GLUCOGAN LIKE PEPTIDE
OTHER HORMONES
Thank You
Sunday, August 11, 2024

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